Efficacy & Safety of Resatorvid in Adults With Severe Sepsis
The purpose of this study is to determine the optimal dose of Resatorvid for reducing 28-day all-cause mortality in subjects with severe sepsis.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Pivotal, Multicenter, Multinational, Randomized, Double-Blind, Placebo-Controlled Study To Evaluate The Efficacy And Safety of TAK-242 in Adults With Severe Sepsis|
- 28-day All-cause Mortality. [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
- Change from Baseline in Organ Failure Assessment [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
- Mean Systemic Inflammatory Response [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
- Mean Vasopressor-free days [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
- Mean Ventilator-free days [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
- Mean Intensive Care Unit free days [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
- Mean Discharge Status. [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
|Study Start Date:||September 2005|
|Study Completion Date:||February 2007|
|Primary Completion Date:||February 2007 (Final data collection date for primary outcome measure)|
|Experimental: Resatorvid 1.2 mg/kg/day||
Resatorvid 1.2 mg/kg, injection, subcutaneously for thirty minutes; then resatorvid 0.05 mg/kg/h (1.2 mg/kg/day), injection, subcutaneously over 96 hours.
Other Name: TAK-242
|Experimental: Resatorvid 2.4 mg/kg/day||
Resatorvid 1.2 mg/kg, injection, subcutaneously for thirty minutes; then resatorvid 0.1 mg/kg/h (2.4 mg/kg/day), injection, subcutaneously over 96 hours.
Other Name: TAK-242
|Placebo Comparator: Placebo||
Resatorvid placebo-matching injection, subcutaneously for thirty minutes; then resatorvid placebo-matching injection, subcutaneously over 96 hours.
Severe sepsis, defined as sepsis associated with acute organ dysfunction, remains a serious medical problem worldwide. In the United States alone, approximately 750,000 cases of severe sepsis occur each year, with the mortality rate ranging between 30% and 50% for severe sepsis patients with concomitant organ dysfunction. As the population ages, these numbers are expected to increase. The pathophysiology of severe sepsis is thought to involve the activation of a variety of inflammatory and procoagulant host responses to infection, which if unchecked, can lead to diffuse endovascular injury, multi-organ dysfunction, and ultimately death.
The host response to infection with microorganism and microorganism-derived molecules is characterized by the synthesis and release of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukins 1, 6 and 8 (IL-1, IL-6, and IL-8), by inflammatory cells, and by other markers of inflammation such as C-reactive protein. Inflammatory cells, such as macrophages, release these cytokines by signals transmitted from the surface of these cells after binding of pathogen-associated molecules to cell surface pattern recognition receptors known as toll-like receptors.
TAK-242 (resatorvid) is a small molecule suppressor of pathogen-induced release of inflammatory cytokines and acts by inhibiting TLR-4 mediated signaling. Because of its inhibitory effect on suppressing cytokine levels, resatorvid is being developed as a treatment for severe sepsis.
The study was ended after the DSMB determined there was insufficient cytokine suppression in the 150-subject analysis within Stage 1 of the study.
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|Study Director:||VP Clinical Science||Takeda|